tbuckley/cabot-search huggingface dataset:
Characteristics of patients with neuroendocrine tumors in the United States: A study of 392,412 patients.
Authors: Ravali A. Reddy, Cheng-I Liao, Caitlin Ruth Johnson, Chunqiao Tian, Kathleen M. Darcy, Daniel Stuart Kapp, John K Chan
Journal: Journal of Clinical Oncology (2022)

10572 Background: To evaluate the characteristics and trends amongst patients with neuroendocrine tumors in the United States. Methods: Data was obtained from the United States Cancer Statistics database from 2001 to 2018. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate characteristics and trends of these cancers per 100,000. The age-adjusted incidences were determined based on the standard population in the United States from 2000. Results: Of 392,412 patients with neuroendocrine tumors, 53.1% were identified in women and 46.9% in men. White, Black, Hispanic, Asian/Pacific Islander and unknown race comprised 73.6%, 14.1%, 7.8%, 2.7%, and 1.7% of the patient population respectively. The majority (64.7%) of tumors originated from the digestive system, followed by 24.5% from the respiratory system. In 2018, the incidence of all neuroendocrine tumors was higher in older (70-79 years) patients as compared to younger (&lt; 50 years) ones at 30.17 vs. 2.79/100,000, in women as compared to men at 8.36 vs. 7.77/100,000, and in White patients as compared to Black, Hispanic, and Asian/Pacific Islander patients (10.82, 10.15, 5.08 and 4.80/100,000 respectively). Amongst different types of neuroendocrine tumors, those originating from the digestive system had the highest incidence at 6.72/100,000 in the year 2018 with colon tumors being the most common subtype. On trend analysis, the groups with the highest annual percent increase included: younger (&lt; 50 years) patients increasing at 5.06%, Hispanic patients rising at 6.44%, and appendiceal tumors increasing at 12.89% per year. On intersection analysis, Black patients between the ages of 70-79 had the highest incidence at 33.39/100,000, while younger (&lt; 50 years) Hispanic patients had the largest increase at 6.22% per year. Conclusions: The incidence of neuroendocrine tumors has increased over our study period. The highest incidence was found in older Non-Hispanic Black patients, with younger Hispanic patients having the highest annual percent increase. Further studies are warranted to better characterize the reasons for these trends and disparities amongst minority patients affected by these tumors.
Immunogenomic characterization of biliary tract cancers: Biomarker enrichment for benefit to immune checkpoint blockade.
Authors: Wungki Park, Fergus Keane, Chaitanya Bandlamudi, Mark Donoghue, Paulino Tallón de Lara, James J. Harding, Danny Khalil, Zoe McKinnell, Michelle Sterpi, Will Cao, Imane H. El Dika, Vinod P. Balachandran, Kevin Soares, Anna M. Varghese, Kenneth H. Yu, David Paul Kelsen, Christine A Iacobuzio-Donahue, Ghassan K. Abou-Alfa, David B. Solit, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2022)

4083 Background: Several immunomodulatory molecules (PD-L1, B7H4, and CD276) have been associated with biliary tract cancer (BTC) subgroups, suggesting potential value to immune checkpoint blockade (ICB) in this lethal disease. Phase II monotherapy (pembrolizumab or nivolumab), and combination (atezolizumab and cobimetinib) ICB trials reported low response rates in unselected advanced BTC with a wide range of responses. A recent randomized phase III trial (TOPAZ-1) reported an overall survival (OS) benefit among patients (pts) with advanced BTC treated with chemotherapy and anti-PD-L1 ICB. However, no correlation between PD-L1 expression and OS was noted and biomarker enrichment strategy in BTC for immunotherapy remains a key to optimize OS. Methods: From our comprehensive clinico-genomic database for BTC at Memorial Sloan Kettering (MSK), a retrospective genomic landscape and neoantigen analysis was performed using MSK-IMPACT. Potential immunogenic subgroups were evaluated: homologous recombination deficiency (HRD) defined by pathogenic alterations in BRCA1/2, PALB2, and BAP1, microsatellite stability high (MSI-H) defined by MSIsensor score ≥10, and tumor mutation burden (TMB)&gt;10. Clinical outcomes with anti-PD-1 ICB were evaluated. Results: Among N=1,190 pts with BTC, N=1,346 samples were sequenced between 03/2014 and 01/2022. Key actionable alterations included (%): IDH1, 2 (13, 3), FGFR2 fusions (9), ERBB2 amplification (5), BRAF V600E (2), RNF43 (2), POLE (2), NTRK1 fusion (&lt;1). There were N=230 (17%) patients with putatively more immunogenic BTC (iBTC) identified by HRD [ BRCA1/2 (1, 2.4), PALB2 (1), BAP1 (9)], TMB&gt;10, and MSI-H. Frequency, location (intrahepatic, ICC; extrahepatic, ECC; gallbladder, GBC), TMB, and genomic instability score (GIS) are summarized (Table). Among iBTC subgroup, N=32 pts received ICB. Their median follow up was 29.1 months. Median lines of prior therapy was 3. Median PFS was 5.6 M (95%CI: 1.2-10.1) and OS was 33.4 M (23.1-43.6). Conclusion: A subgroup of BTC pts (iBTC) benefit from ICB. Apart from MSI-H and TMB&gt;10, other genomically-defined subgroups such as HRD may benefit from ICB. Prospective studies are needed to evaluate a better biomarker enrichment strategy beyond PD-L1 and TMB, that can represent other immunogenic aspects of tumor neoantigen and microenvironment. [Table: see text]
Not just biology: Comparing social determinants of health in patients diagnosed with late-stage lung, breast, and colon cancer.
Authors: Dena Rhinehart, Jessica Lozier, Gerard A. Silvestri
Journal: Journal of Clinical Oncology (2022)

e18582 Background: Lung, colorectal, and breast cancer account for the majority of cancer deaths in the U.S. Patients with late stage lung cancer have the shortest survival of the three, and lung cancer patients are more likely to be diagnosed at later stages. We undertook this study to compare social determinants of health in patients diagnosed with late stages of lung, breast, and colon cancer to assess the impact they have on health and mortality. Methods: Data from the National Cancer Database was used for this study. We compared factors including insurance, income, and residency among late stage cancer patients (Stage III and IV). We also compared baseline health status measured by comorbidity index. Descriptive statistics were used to compare patient characteristics. Statistical significance was determined on the basis of a two-sided p value &lt; 0.05. All statistical analysis was performed using SAS, version 9.4. Results: Between 2004 - 2016, 3,005,513 patients were diagnosed with lung (1,004,999), breast (1,309,796), and colon (690,718) cancer. The racial make-up of the groups was similar. 72.5% of lung cancer patients were diagnosed at late stage compared to 48.8% of colon and 13.8% of breast cancer patients. Patients with late stage lung cancer were more likely to have income &lt; $38,000, reside in rural locations, and less likely to have private insurance. Late stage lung cancer patients were 2 and 4 times more likely to have at least 2 comorbidities than patients with colon and breast cancer respectively. Conclusions: Patients with lung cancer are disproportionately affected by several negative social determinants of health. The association between smoking and lung cancer may help explain this because the highest smoking rates in the U.S. occur in populations with lower income, low education status, less insurance coverage, and significantly more comorbidities (e.g. COPD, Heart Disease). These patients are dealing with the complex interplay of negative social determinants of health and worse baseline health status causing delays in diagnosis and treatment when compared to other cancers. Recognizing this may allow systems to better support this disadvantaged population and improve access to screening, clinical trial inclusion, and personalized treatment options while working longitudinally to reverse the systemic factors affecting disproportionate tobacco use and lack of healthcare access in for this underserved population.
CD47 expression patterns in thymic epithelial tumors.
Authors: Thomas Yang Sun, Brandon Nguyen, Simon Chen, Yasodha Natkunam, Sukhmani Kaur Padda, Matt Van De Rijn, Heather A. Wakelee, Jonathan W. Riess
Journal: Journal of Clinical Oncology (2022)

8586 Background: Blockade of CD47, an immunoglobulin overexpressed on solid tumor cells that inhibits macrophage phagocytosis, is a promising anti-cancer immunotherapy which has not yet been explored in thymic epithelial tumors (TETs). TETs, including thymomas and thymic carcinomas, are rare tumors with limited immunotherapy treatment options due to the high rates of immune-related adverse effects observed with PD-1/PD-L1 checkpoint inhibitors. This study aimed to examine CD47 protein expression in TETs. Methods: A clinically annotated tissue microarray of 67 TETs consisting of 64 thymomas and 3 thymic carcinomas, as well as 14 thymic controls were included. Each sample with an average of 3 cores was stained for CD47 epithelial expression (rabbit monoclonal antibody SP279, Abcam, USA). Samples were scored for intensity as follows: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. An H-score, defined as intensity x percentage of tumor involved, was also assigned and ranged from 0 to 300. Samples with an intensity score of &lt; 2 or an H-score of &lt; 150 were categorized as CD47 low , while the rest as CD47 high . Multivariate linear regression analysis accounted for WHO subtype, stage, resection status and presence of paraneoplastic syndrome (Prism 9, Graphpad). Results: Compared to normal thymic tissue, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was present in 91% of TETs, compared to 64.3% of normal thymus. Importantly, the level of expression was significantly higher in TETs by 16-fold (mean H-score 75.0 vs 4.6, p = 0.003). Among tumors, univariate analyses showed that higher CD47 expression was correlated with a lower stage (p = 0.032) and more complete resection (p = 0.058). A multivariate analysis accounting for these factors showed that CD47 expression by both H-score and intensity were each highly correlated with WHO histology subtype (p = 0.0005; p = 0.0017 respectively) with lower grade subtypes more frequently found in CD47 high tumors. The most frequent subtype in CD47 high , when compared to CD47 low tumors, was AB (61.5% vs 13.7%) and the least frequent was B2 (0% vs 37.3%). Tumors with the highest grade (subtype C, thymic carcinomas) were exclusively CD47 low . CD47 high tumors were associated with an increased incidence of paraneoplastic syndromes (52.4% vs 12.0%, p = 0.0014). Conclusions: CD47 expression was found in the vast majority of TETs, and in significantly higher levels than normal thymic tissue. Among tumors, those with higher CD47 expression tended to have lower grade and stage, as well as higher frequency of paraneoplastic syndromes. This study is the first to examine CD47 expression in TETs. Given the prevalent expression of CD47 found in TETs and current available CD47 targeted agents, this study lends support for further investigation of this novel therapeutic approach.
Clinicopathologic and mutational landscape of <i>BRAF</i><sup>V600E</sup>-mutant non–small cell lung carcinoma.
Authors: Jane Sze Yin Sui, Marc Ladanyi, Charles M. Rudin, Alexander E. Drilon, Gregory J. Riely, Mark G. Kris, Michael Offin
Journal: Journal of Clinical Oncology (2022)

9084 Background: BRAF mutations (mts) occur in 2-5% of non-small cell lung cancers (NSCLC) with approximately 50% being BRAF V600E . Limited data is known regarding the mutational landscape (ML) and prognostic role of co-mutations in BRAF V600E NSCLC. We performed this study to evaluate clinicopathological characteristics and the impact of ML in BRAF V600E NSCLC. Methods: Patients (pts) with BRAF V600E mutant NSCLC were identified using MSK-IMPACT at Memorial Sloan Kettering Cancer Center between January 2014 to October 2021. Baseline clinicopathological characteristics and treatment outcomes were annotated. Due to the enrichment of SETD2 in BRAF V 600E NSCLC, we conducted further analyses using cbioportal to identify co-mutations of SETD2 with other actionable mutations in NSCLC. Overall survival (OS) was assessed from the date of metastatic disease until death using the log-rank test. Results: BRAF mutations were detected in 5% of NSCLC samples (512/10220) with 22% (97/435 pts) being BRAF V600E . Of the 97 pts with BRAF V600E NSCLC identified: 57 pts (59%) were females, median age of 68 (range: 38-93 years), 58 pts (60%) were former smokers. All BRAF V600E tumors were adenocarcinoma and the median tumor mutational burden was 5 mt/Mb (range: 0-40). 46 pts (48%) with BRAF V600E NSCLC were diagnosed with de novo metastatic disease. Pts receiving targeted therapy at first, second, and subsequent lines of therapy numbered 17 (29%), 18 (31%), and 10 (17%) respectively. Co-alterations of BRAF V600E with TP53 and SETD2 were found in 45% (44/97) and 42% (41/97), respectively. There is a much lower prevalence of concurrent inactivating SETD2 mutations than with other actionable alterations in NSCLC: ROS1 (9%), ALK (8%), RET (8%), HER2 (6%), MET (5%), KRAS (5%), EGFR (2.9%) and BRAF non-V600E (2%). Median OS in BRAF V600E+ / TP53 + vs BRAF V600E+/ SETD2 + were 35 vs 36 mos (HR 0.88m 95% CI 0.45-1.75, P= 0.71) and BRAF V600E+/ TP53 + / SETD2 + vs BRAF V600E+ / TP53 - / SETD2 - were 19 vs 39 mos (HR 0.37, 95% CI 0.09-1.50, P= 0.06). Conclusions: Among the BRAF V600E lung adenocarcinomas, concurrent TP53 mutation and SETD2 inactivation define a patient subset with significantly shorter overall survival. Further studies are warranted to investigate the role of SETD2 mutations in the context of BRAF V600E in NSCLC pts.
Improving resident education on the inpatient solid tumor oncology rotation through development of an asynchronous video curriculum.
Authors: Laura Walsh, Parul Agarwal, Sam Brondfield, Natasha Chida, Ross C. Donehower, Kristen Marrone
Journal: Journal of Clinical Oncology (2022)

e23014 Background: As the oncology patient population grows, continued recruitment of talented individuals is essential. Meaningful and highly educational clinical exposures play a crucial role in a resident’s decision to pursue fellowship in oncology. Currently, the majority of oncology exposure occurs in the inpatient setting, where trainees are confronted with many competing clinical demands, leaving minimal time for teaching. Prior work has demonstrated that dedicated time for teaching supplemented with high-yield educational material improves trainee satisfaction and interest in a particular field. We hypothesize that implementing an asynchronous inpatient video oncology curriculum will improve resident clinical competency and satisfaction. Methods: This is an ongoing, single institution educational intervention using the Kern method for curriculum development in the Johns Hopkins Osler Internal Medicine Residency (IRB00307077). A targeted needs assessment has been developed to identify gaps in medical knowledge, assess preparedness in managing common solid tumor inpatient diagnoses, and explore satisfaction with prior educational experiences on this service. Based on these results, ten educational videos will be created by content experts and aligned with the learning objectives of the Osler residency program and ABIM blueprint. Trainees will have dedicated time to watch the videos during their solid tumor rotation. We plan to evaluate effectiveness of our curriculum by measuring completion rates and pre- and post-video multiple choice responses. We will also assess knowledge retention and resident satisfaction at three and six months post-rotation with online questionnaires. Results: Annual Osler program ACGME survey data review revealed a high level of resident dissatisfaction with the oncology clinical experience compared with other rotations. While 83.3% of residents rated their general internal medicine experience as “excellent,” only 52.4% rated their oncology experience as “excellent.” Needs assessment data collection has been delayed by the COVID-19 pandemic but is ongoing. Following topic selection, videos will be created in April 2022 with plans for video curriculum implementation in July 2022. Conclusions: In order to attract and retain trainees in the field of oncology, it is imperative that educational curricula adapts to meet learners’ needs. Efficient, evidence-based instructional strategies designed to promote clinical competency for internal medicine residents on an inpatient solid tumor service may foster engagement and rotation satisfaction. We are currently evaluating how an asynchronous video inpatient oncology curriculum may significantly improve the inpatient internal medicine trainee experience. If successful, this curriculum can be adapted for other trainees and practitioners new to the field of oncology.
Animal Models to Study Cardiac Arrhythmias
Authors: Daniel J. Blackwell, Jeffrey Schmeckpeper, Bjorn C. Knollmann
Journal: Circulation Research (2022)

Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide, accounting for 10% to 15% of all deaths. Although most arrhythmias are due to acquired heart disease, inherited channelopathies and cardiomyopathies disproportionately affect children and young adults. Arrhythmogenesis is complex, involving anatomic structure, ion channels and regulatory proteins, and the interplay between cells in the conduction system, cardiomyocytes, fibroblasts, and the immune system. Animal models of arrhythmia are powerful tools for studying not only molecular and cellular mechanism of arrhythmogenesis but also more complex mechanisms at the whole heart level, and for testing therapeutic interventions. This review summarizes basic and clinical arrhythmia mechanisms followed by an in-depth review of published animal models of genetic and acquired arrhythmia disorders.
A multicenter, randomized, double-blind phase III clinical study to evaluate the efficacy and safety of KN046 combined with nab-paclitaxel and gemcitabine versus placebo combined with nab-paclitaxel and gemcitabine in patients with advanced pancreatic cancer (ENREACH-PDAC-01).
Authors: Gang Jin, Shiwei Guo, Jianming Xu, Rongrui Liu, Qianqian Liang, Yong Yang, Baohong Guo, Yiqi Xu, Binyan Xia, Chao Zhang, Shengxia Zhu, Ting Xu
Journal: Journal of Clinical Oncology (2022)

TPS4189 Background: Pancreatic cancer is biologically aggressive, and the majority of pts was diagnosed as locally advanced or metastatic disease. Nab-paclitaxel and gemcitabine is a frequently used regimen for advanced pancreatic cancer, but chemoresistance is unavoidable. The combination of immunotherapy with chemotherapy have shown efficacy for certain types of cancer, but no similar results have been obtained in pancreatic cancer. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 and CTLA-4 pathways and restore T-cell immune response to tumor. In a phase Ⅱ clinical trial (NCT04324307), as of August 10, 2021, 53 pts with unresectable advanced pancreatic cancer had received one cycle KN046 combined AG regimen treatment and 31 subjects had received post-baseline tumor assessment at least once. Objective response rate (ORR) was 45.2% (95% CI: 27.3%, 64.0%) and disease control rate (DCR) was 93.5% (95% CI: 78.6%, 99.2%)，excellent preliminary results have been achieved. Based on this, a phase III pivotal study (ENREACH-PDAC-01) is conducting now in China to verify the efficacy and safety of KN046 plus nab-paclitaxel and gemcitabine as first-line treatment for advanced pancreatic cancer (NCT05149326). Methods: This nationwide multicenter phase III clinical trial enrolled pts with histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic ductal adenocarcinomas with a WHO performance score of 0 or 1 and expected survival period of more than 3 months. Eligible pts will be randomized 1:1 to intervention group or control group and receive 4-6 cycles of KN046 (5mpk Q2W) or placebo combined with nab-paclitaxel (initial dose: 125mg/m 2 D1,8,15 Q4W) and gemcitabine (initial dose: 1000mg/m 2 D1,8,15 Q4W) followed by KN046 (5mpk Q2W) or placebo with gemcitabine（QW × 3, 1 week off） maintenance therapy. Treatment will continue until disease progression or intolerable toxicity, withdrawal of consent, loss to follow-up or death, end of study, whichever occurs first. The primary endpoint is overall survival (OS). Key secondary endpoints are ORR and progression free survival (PFS). PFS and ORR will be assessed independently per RECIST v1.1 at screening, every 8 weeks for 1 year and then every 12 weeks until disease progression. Tumor and blood samples will be collected at baseline and during study treatment for pharmacokinetic, immunogenicity and biomarker assessment. The first patient was enrolled in early February 2022. Clinical trial information: NCT05149326.
Treatment patterns and outcomes associated with small cell lung cancer by platinum sensitivity status in a U.S. Medicare population.
Authors: Paul Cockrum, Joanna P. MacEwan, Robert A. Ramirez
Journal: Journal of Clinical Oncology (2022)

e20617 Background: Platinum-based chemotherapy plus irinotecan or etoposide is the standard of care for first line (1L) treatment of small cell lung cancer (SCLC). Sensitivity to platinum-based chemotherapy has implications for regimen choice in subsequent lines of treatment. The goal of this study was to examine differences in patient characteristics, treatment patterns, and survival associated with the management of SCLC in a Medicare population by platinum sensitivity status, i.e., platinum sensitive (PS) or platinum refractory (PR). Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data. Patients were included if they had a record with a diagnosis of SCLC in the database from 1/1/2007 – 12/31/2017 and were ≥65 years of age at diagnosis. Patients also had continuous enrollment for ≥180 days pre-SCLC diagnosis and platinum-based 1L treatment. Patient characteristics, treatment patterns, and outcomes were stratified by PS status, which was defined as initiating 2L therapy more than 6 months after the last administration of platinum-based chemotherapy in 1L. Median overall survival (OS) was estimated using the Kaplan Meier method. Results: 7,208 patients met the study criteria and one in three (33.6%, N = 2,424) SCLC patients were PS. The PS population was majority female (64.4% vs 35.6% males), younger on average (aged 72.4 yrs vs 72.9 yrs), and more likely to be diagnosed at stage I-III than the PR patient population (50.6% vs 21.1%). Among PS patients, mean time from diagnosis to 1L treatment was 6.1 weeks versus 5.7 weeks among PR patients. Only 29.7% of PS patients initiating 1L went on to second line (2L) versus 40.4% of PR patients. 68.6% of PR patients received monotherapy in 2L, with topotecan (31.7%), paclitaxel (12.1%), and irinotecan (9.9%) being the most common monotherapy regimens. 51.7% of PS patients were retreated with platinum-based chemotherapy in 2L. Median OS from initiation of 1L was 20.2 months (95%CI: 19.3-21.1 months) among PS patients versus 6.4 months (95%CI: 6.2-6.6 months) among PR patients. 5-year survival was 20.0% among PS patients and 1.5% among PR patients. Conclusions: Approximately two-thirds of SCLC patients are refractory to platinum-based chemotherapy. These patients have fewer treatment options and shorter OS than PS patients, underscoring the ongoing need for effective therapies for SCLC.